Project Summary. Our long-term goals are to clinically translate in vivo imaging tools for the improved management of cancer patients. Our primary focus in this project is developing and using nanotechnology imaging for prostate cancer biopsy and management. In particular, we focus on ultrasound and photoacoustic imaging. There is already an advanced landscape of ultrasound imaging including transrectal ultrasound imaging used to manage prostate cancer. Our work will expand this to photoacoustic imaging. This allows imaging of not only the disturbed vasculature associated with cancer, but adding nanoparticle contrast agents will transform this approach from anatomic imaging to molecular imaging. Although we focus on prostate cancer here, we expect that our strategies will eventually apply to many other cancers studied with ultrasound including liver, ovarian, pancreatic, etc. We have made significant progress over the last cycle of this CCNE competing renewal grant including the development of photoacoustic molecular imaging hardware that has already been evaluated in humans. We will continue to study how our in vivo imaging strategies can be improved even further through use with in vitro diagnostics. Indeed, both in vitro nanosensors and in vivo nano-molecular imaging will be utilized to accomplish our long-term goals. The combination of both in vitro and in vivo diagnostic strategies is expected to lead to a much greater accuracy and cost-effectiveness than either strategy alone. To translate our in vitro and in vivo diagnostic strategies we will utilize mouse models of human cancer that help us to test our approaches prior to clinical translation. The clinical translation will be accomplished through the help of the clinical translation core (Core 2) which links to various clinical trials and leverages on other funding mechanisms already in place in our CCNE.